1-37810130-T-C

Position:

• chr1-37810130-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005955.3(MTF1):​c.*5006A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,194 control chromosomes in the GnomAD database, including 35,466 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (35420 hom., cov: 32)
  • Exomes 𝑓: 0.78 (46 hom.)
• Consequence: MTF1 NM_005955.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

Genes affected

MTF1 (HGNC:7428): (metal regulatory transcription factor 1) This gene encodes a transcription factor that induces expression of metallothioneins and other genes involved in metal homeostasis in response to heavy metals such as cadmium, zinc, copper, and silver. The protein is a nucleocytoplasmic shuttling protein that accumulates in the nucleus upon heavy metal exposure and binds to promoters containing a metal-responsive element (MRE). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF1	NM_005955.3	c.*5006A>G		3_prime_UTR_variant	11/11	ENST00000373036.5	NP_005946.2
MTF1	XM_011541491.3	c.*5006A>G		3_prime_UTR_variant	11/11		XP_011539793.1
MTF1	XM_047421170.1	c.*5006A>G		3_prime_UTR_variant	12/12		XP_047277126.1
MTF1	XM_047421173.1	c.*5006A>G		3_prime_UTR_variant	10/10		XP_047277129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5	c.*5006A>G		3_prime_UTR_variant	11/11	1	NM_005955.3	ENSP00000362127	P1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103755 AN: 151928 Hom.: 35372 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.682

GnomAD4 exome AF: 0.784 AC: 116 AN: 148 Hom.: 46 Cov.: 0 AF XY: 0.773 AC XY: 68 AN XY: 88

Gnomad4 FIN exome AF: 0.804

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.683 AC: 103854 AN: 152046 Hom.: 35420 Cov.: 32 AF XY: 0.685 AC XY: 50910 AN XY: 74308

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.676

Alfa AF: 0.678 Hom.: 56882

Bravo AF: 0.667

Asia WGS AF: 0.693 AC: 2412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs473279; hg19: chr1-38275802; COSMIC: COSV65988606; COSMIC: COSV65988606;